We propose to study the regulation of lymphokine secretion in subsets of helper T cells. We have substantial evidence that two subsets of helper T cells exist and that those T cells are able to secrete IL4 and IL5 (Th2) develop only after priming. (1) We will characterize and compare the subpopulations of normal helper T cells which secrete the lymphokines IL2 and IFN gamma (Th1) versus those which secrete IL4 and IL4 (Th2). We will study the kinetics of their appearance and the requirements for their induction including the lymphokines which regulate their development. We will also delineate the phenotype of their precursors. (2) We will determine the frequency of the two types of helpers among populations of lymphoid cells derived from different lymphoid organs both before and after priming using biological assays and by detecting cell synthesizing lymphokines by fluorescent staining. (3) We will use both immunological techniques and molecular assays to investigate the in situ production of lymphokines by T cells in normal mice undergoing an immune response. We will study the kinetics of development and the distribution of lymphokine- secreting T cells during an immune response. Characterization of T cells secreting distinct lymphokines which have different effects on the multiple cells involved in immune response will provide valuable information about the regulation of the immune response which is necessary for the development of effective immunotherapy.